Growing evidence suggests that the transforming growth factor b (TGF-b) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGFb1 and its receptor TGF-bRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C-509T and Leu10Pro polymorphisms in TGFB1 and G-875A variant in TGFBR2, using the primer-introduced restriction analysis (PIRA)-PCR assay, in a case-control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C-509T and TGFBR2 G-875A, were associated with a significantly decreased risk of gastric cancer [adjusted odds ratio (OR) 5 0.65, 95% confidence interval (CI) 5 0.52-0.82 for 2509CT/TT and adjusted OR 5 0.67, 95% CI 5 0.53-0.85 for 2875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C-509T and TGFBR2 G-875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR 5 0.44, 95% CI 5 0.32-0.62). These findings indicate, for the first-time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility. ' 2006 Wiley-Liss, Inc.

Background. L-carnitine has been used for several years as an adjuvant therapy in oxidative stress, blood sugar, high-sensitivity C-reactive protein (CRP), anemia, etc. However, the efficacy of L-carnitine treating insulin resistance (IR) remains controversial. Homeostasis model assessment of Insulin Resistance (HOMA-IR) is widely used in the clinical evaluation of patients with IR. Objectives.A meta-analysis, including randomized controlled trials (RCTs), was performed to assess the effect of L-carnitine on HOMA-IR patients.Material and methods. The Cochrane Library, PubMed, and EMBASE databases were systematically searched to identify RCTs which evaluated the effects of L-carnitine on HOMA-IR patients. We screened relevant studies according to predefined inclusion and exclusion criteria. In the selected articles, we extracted the data: study design, sample size, age, L-carnitine dose and regimen, body mass index (BMI) of patients, mode of administration, study duration and study outcomes.Results. A total of 5 studies were included for the meta-analysis. The result showed L-carnitine was useful in the treatment of IR (WMD -0.724, CI -0.959 -0.488, p < 0.0001). Evaluation at 3, 6, 9, 12 months, the p-values were 0.875, 0.165, 0.031, 0, 007, respectively.Conclusions. L-carnitine was useful in treating patients with IR. L-carnitine can treat IR more effectively with prolonging the medication time. However, more RCTs with long-term L-carnitine treatment of IR are needed to confirm the viewpoint.

Purpose: Accumulative evidence suggests that folate has a protective effect on gastric cancer.The methylenetetrahydrofolate dehydrogenase (MTHFD) plays an important role in folate and homocysteine metabolisms, and polymorphisms of MTHFD may result in disturbance of the folate-mediated homocysteine pathway. The aim of this study is to test the hypothesis that genetic variants of MTHFD and plasma homocysteine levels are associated with risk of gastric cancer and modulated by genotypes of methylenetetrahydrofolate reductase (MTHFR). Experimental Design: We genotyped G1958A and T401C in MTHFD and C677T in MTHFR and detected total plasma homocysteine (tHcy) levels in a case-control study of 589 gastric cancer cases and 635 cancer-free controls in a high-risk Chinese population. Results: The variant genotypes of MTHFD 1958AA and 401CC were associated with a significantly increased risk of gastric cancer [adjusted odds ratio (OR), 2.05; 95% confidence interval (95% CI), 1.34-3.13 for 1958AA; adjusted OR, 1.43; 95% CI, 1.14-1.80 for 401CC] compared with 1958GG/GA and 401TT/TC genotypes, respectively. Both of the effects were more evident in the subjects carrying MTHFR 677CT/TTgenotypes. The average tHcy level was significantly higher in gastric cancer cases than in controls (P < 0.01), and the upper quartile of tHcy (>13.6 Amol/L) was associated with an 82% significantly increased risk of gastric cancer, compared with the lowest quartile of tHcy (V8.0 Amol/L; adjusted OR, 1.82; 95% CI, 1.20-2.75). Conclusions: The strong associations between MTHFD variants and the plasma tHcy levels and gastric cancer risk suggest, for the first time, a possible gene-environment interaction between genetic variants of folate-metabolizing genes and high tHcy levels in gastric carcinogenesis.

It is commonly thought that even a moderately high ionic concentration in the background electrolyte (BGE) would lead to Joule heating and serious peak distortion. However, we obtained very satisfactory separations of both inorganic and organic anions in electrolyte solutions as high as 5 M sodium chloride using direct photometric detection. Samples containing a 0.5 M concentration of a salt can be analyzed directly by making the BGE concentration of the same salt even higher to obtain electrostacking. The temperature in the center of the capillary was calculated to be 49 degrees C when the current is at its maximum of 280 microA. The effect of various salts on electrophoretic and electroosmotic mobility is discussed. Several examples are given of capillary electrophoresis under high-salt conditions.

These results are consistent with our previous findings in gastric cancer and support the hypothesis that genetic variants in TGFB1 and TGFBR2 may modulate the risk of ESCC.

Epidermal growth factor (EGF), a ligand of the EGF receptor, plays a critical role in the development of gastric cancer. Genetic variants in its promoter region may influence transcription activity and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped three EGF promoter polymorphisms (G61A, G-1380A, and A-1744G) in a case-control study of 675 gastric cancer cases and 704 cancer-free controls. We found that the variant genotypes of EGF 61GA/AA were associated with a significantly decreased risk of gastric cancer (OR = 0.77, 95% CI = 0.61-0.95), when compared with wild-type homozygote 61GG. In the combined analysis with all three loci of EGF, subjects carrying one or more variant loci had a significantly decreased risk of gastric cancer in a dose-response manner ( G astric cancer is the second leading cause of cancer-related mortality worldwide, accounting for ~700 000 deaths annually.(1) Almost 40% of the gastric cancer cases occur in China with a remarkable geographic variation.(2) Epidemiological studies suggest that some environmental exposures (e.g. salty diet, tobacco smoking and Helicobacter pylori infection) are important for the development of gastric cancer.(3,4) However, accumulating evidence indicates that host factors and genetic alterations may also play an important role in gastric carcinogenesis through gene-environment interactions. The EGF gene encodes a ligand for the EGFR, a receptor of tyrosine kinase. When binding with EGFR, EGF can activate multiple signaling pathways, regulating cell proliferation and differentiation.(6-9) Studies showed that EGF and EGFR were highly expressed in gastric cancer, (10,11) cooperating with H. pylori and inflammatory cytokines in gastric carcinogenesis. (12,13) Shahbazi et al. analyzed the EGF gene region from position -1350 to 164 and identified a G to A substitution at position 61 in the 5′ untranslated region, where the presence of the variant 61 A allele leads to a decreased in vitro EGF production in peripheral blood mononuclear cells. (14) Therefore, it was hypothesized that this promoter variant might be associated with risk of gastric cancer. In a hospital-based case-control study in Japan (200 cases and 230 controls), Hanai et al. reported that EGF G61A (rs4444903) was involved not only in the occurrence but also in the progression of gastric cancer.(15) However, this result was not supported by a later study in Japan (202 cases and 454 controls), although the main effect of EGF G61A was in the same direction. (16) Because the single locus may not represent the functional region of the gene promoter, it is biologically possible that other promoter variants may be also involved in gastric cancer susceptibility through a haplotype effect. Therefore, we used the public SNP database (http://www.ncbi.nlm.nih.gov/) to select SNPs in the promoter region of EGF. Apart from G61A, we chose two SNPs, G-1380A (rs11568835) and A-1744G (rs3756261), with a minor allele frequency >0.05 in a Chinese population.To evaluate the effects of...

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We have demonstrated, for the first time, that capillary electrophoresis (CE) can be interfaced with low-temperature fluorescence line-narrowing (FLN) spectroscopy for on-line structural characterization. Detection by laser-induced fluorescence spectroscopy, under fluorescence non-line-narrowing and line-narrowing conditions, provides three-dimensional electropherograms and FLN spectra, which lead to significantly improved overall resolution and allow for structural characterization ("fingerprinting") of molecular analytes. This novel CE-FLN system consists of a modular CE system, instrumentation for FLN spectroscopy, and a specially designed capillary cryostat (CC). An absorbance detector serves to determine the migration rates of analytes. After the 77 K fluorescence-based electropherogram is generated, the temperature of the capillary is lowered to 4.2 K for high-resolution FLN characterization. Automated translation of the CC and capillary in the direction of the capillary axis allows the separated analytes to be sequentially characterized by fluorescence spectroscopy as the capillary is translated through the laser excitation region. Detection of fluorescence from stationary CE-separated analytes significantly improves the accuracy of quantitation and structural characterization. We believe that this interfacing represents an exciting addition to the rapidly evolving field of CE, providing a new and powerful tool for chemical analysis. The first application of the CE-FLN system to a mixture of polycyclic aromatic hydrocarbons is presented; prospects and future applications of CE-FLN are briefly addressed.